Medical tape is used to hold essential devices to the skin for long periods of time. Unfortunately, without means for safe removal, these strong adhesives are painfully removed from the skin, often resulting in medical adhesive-related skin injuries (MARSI). Initial stakeholder interviews have indicated that medical tape removal is painful for the patient, and causes significant anxiety for nurses and caregivers. A 2015 study showed 98.6% of nurses considered skin tears common, occurring in 15% of senior patients and 17% of neonatal patients. A medical tape that offers high adhesion with means for safe removal is needed to eliminate MARSI and increase quality of care. UnTape addresses this need by providing a medical tape that has high adhesion during use but allows for easy and injury-free removal, by simply heating the tape for a few seconds with a heat pack prior to removal. The result is a rapid reduction of the force needed to remove the tape from the patient’s skin without risking MARSI. The tape is formulated with pressure-sensitive adhesive (PSA) that contains an embedded temperature-responsive additive (TRA). The additive will migrate to the surface of the tape upon heating, and melt in the range of 38-43°C, forming puddles that disrupt the adhesive and skin interface. The TRA is selected with a melting temperature that is high enough to avoid accidental peel strength reduction during fever, but below the pain threshold (45-47°C) for skin. Different additives have exhibited over a 50% reduction in peel force. This work focuses on optimization of product definition to yield consistent in vitro testing results, paving the way to clinical studies. The unique properties of UnTape allow for stronger skin adhesion for critical medical devices while eliminating the risk of MARSI upon removal, reducing nurse and patient stress, and providing higher quality medical care.

Personalized medicine, enabling each patient to receive earlier diagnoses, risk assessments, and optimal treatments hold promise for improving cancer health care while also lowering costs. For example, more than 60% of breast cancers (BC) in women are diagnosed as estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-), which is then typically treated with adjuvant therapy that combines endocrine therapy with CDK4/6 inhibitors (CDK4/6i). In addition to high cost, CDK4/6i treatment time can increase particularly within the <50% patient population that experiences drug resistance and who must proceed to a second line of treatment. Exosomes are membrane-bound extracellular vesicles that have recently demonstrated rapid growth in BC research due to their vast array of tissue-specific surface markers and molecular contents that can be used to confirm a prognosis. For example, overexpression of exosomal TK1 is associated with CDK4/6i resistance; thus, exosomal cargo content can be analyzed to enable tailored treatment with the best response and highest safety margin for ER+/HER2- BC patients. However, exosome heterogeneity has hindered research progress due to lagging analytical techniques to effectively characterize and isolate BC-specific exosomes. This project combines an oligonucleotide hybridization reaction with temperature-sensitive polymer-oligonucleotide conjugates that can detect and rapidly isolate specific exosome subtypes depending on tissue-specific exosome surface proteins. We expect that the isolated exosome cargo will quantitatively demonstrate susceptibility or building resistance to CDK4/6i. Future work includes optimizing the oligonucleotide sequence, further pinpointing target BC-specific surface markers, testing the assay, and comparing results to current methodologies. Ultimately, enabling an exosome liquid biopsy method to tailor patient-specific BC treatments can decrease the overall time, cost, and toxicity associated with current non-specific cancer treatment methods and can also be utilized in monitoring dynamic cancer metastasis.

Hydrogels, water-swollen materials made of polymer networks, replicate the chemical and structural signals that influence cells growing in vivo, allowing researchers to control stimuli and study cell behavior outside of the body. In vivo, cells grow in curved environments, which provide additional cues that influence cell differentiation and behavior. The goal of this project is to develop a hydrogel where curvature can be activated by allowing contractile cells to compact the hydrogel in a spatially controlled manner. To achieve this, we synthesized a cyclic crosslinker peptide that acts as a two-input Boolean AND gate, with one arm of the cycle degradable by cell-secreted enzymes and the other arm degradable by user-administered transpeptidase. This crosslinker forms gels that dissolve in response to both stimuli, but not in response to either individually. In a cell-adhesive hydrogel polymerized by this crosslinker, we predict that curvature can be activated in hydrogels upon user addition of exogenous transpeptidase, due to an increase in cell spreading and macroscopic contraction. Once the hydrogel system behaves as designed, we intend to investigate the response of cardiac cell types to tissue curvature in a controlled environment, in order to unveil the mechanisms by which the geometric cue impacts disease and development. This understanding can help researchers identify possible drugs that target signals from tissue curvature, and in regenerative medicine, it can help inform how tissue is grown in vitro to better match native tissue.

Reactive oxygen species (ROS) are metabolites which play a critical role in biological systems. The deregulation of ROS creation and reduction damages proteins, lipids, and DNAs. Specifically, hydrogen peroxide (H2O2) is a key molecule known for its significant role in the various physiological processes impacted by cellular redox dynamics. However, there is a lack of tools with the sensitivity, dynamic range, and kinetics necessary for researchers to measure intracellular H2O2 levels. Our lab previously developed a genetically encoded fluorescent indicator for the real-time monitoring of H2O2 dynamics to address this need. Genetically encoded fluorescent indicators are protein-based sensors that allow researchers to visualize the activity of important molecules and understand the mechanisms by which critical physiological pathways operate in living systems. These sensors have great advantages as tools for quantifying molecular activity, including high spatiotemporal resolution, subcellular specificity, and minimal invasiveness. Our green-fluorescent H2O2 sensor HRM63 demonstrated 50-times faster onset and 10-times higher sensitivity for H2O2 when compared to the current state-of-art redox sensor HyPerRed – a significant improvement. I strive to expand the fluorescent palette of H2O2 sensors based on the design of HRM63 in order to enable the multiplexed imaging necessary to capture the dynamic pathophysiological processes which involve ROS. I have taken a structure-guided protein design approach and applied molecular cloning techniques to develop and iteratively optimize red-shifted versions of HRM63 with longer excitation/emission wavelengths, which would allow for deeper penetration of light source and fluorescence. I validate the performance of prototype sensors by applying fluorescence microscopy techniques to image their responses to applied concentrations of H2O2 in models of human disease. By optimizing these sensors, we will create invaluable tools for researchers to study the pathophysiology of the wide range of diseases to which ROS are linked, including cardiovascular diseases, neurodegenerative diseases, and cancer.

Antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) can treat and prevent Human Immunodeficiency Virus (HIV), respectively. However, good medication adherence (≥4 doses/week) is crucial for these treatments to work effectively. Our research group recently developed the REverse TranscrIptase Chain Termination (RESTRICT) assay, a rapid enzymatic assay that measures the amount of tenofovir diphosphate (TFV-DP) present in blood, a drug that is a good indicator of long-term (1-3 month) ART/PrEP adherence. The goal of this project is to modify RESTRICT to additionally measure the amount of emtricitabine triphosphate (FTC-TP) in blood, which serves as a good indicator of short-term (1 week) adherence. RESTRICT provides the HIV reverse transcriptase (HIV RT) enzyme all the required reagents for synthesizing double-stranded DNA (dsDNA) and measures the concentration of TFV-DP and FTC-TP based on their inhibition of HIV RT activity. We designed custom DNA templates that bind preferentially to either TFV-DP or FTC-TP based on the nucleotides that they mimic. We also designed molecular beacon probes with different fluorescence dyes that bind to each DNA template and can provide fluorescence output corresponding to the amount of complementary DNA (cDNA) synthesized by HIV RT. High drug levels will lead to less cDNA synthesis and lower fluorescence intensities, indicating good adherence to treatment. Preliminary results indicate that molecular beacon probes can distinguish between the cDNA associated with each drug, which would allow for the simultaneous detection of TFV-DP and FTC-TP in a single reaction tube through the fluorescence measurements of the two types of dyes. Ongoing work is focused on optimizing RESTRICT reactions to measure clinically relevant concentrations of TFV-DP and FTC-TP. Gaining information about long- and short-term adherence to treatment through the detection of TFV-DP and FTC-TP respectively, would allow for more informed interventions by healthcare professionals to help patients improve adherence, leading to better health outcomes.